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Cells' Exit Signs

by Kathleen Cason



Like miniature factories, cells manufacture products in specialized compartments and ship them where they’re needed. Motor proteins — the cell’s version of 18-wheelers — then haul the cargo along “highways” made of protein fibers called microtubules. But how do motor proteins know where to go?

An international research team recently identified a new group of enzymes that may help uncover how cells direct their internal traffic. The team is co-led by Jacek Gaertig, professor of cellular biology at the University of Georgia, and Bernard Eddé of the National Center for Scientific Research in Montpellier, France. They published their findings in the June 17, 2005, issue of Science.

The newly discovered enzymes, called polyglutamylases, attach an unusual molecular tag to microtubules. “We’ve known for more than a decade that strings of glutamic acid [an amino acid] are sometimes attached to the side of a protein called tubulin [a component of microtubules],” Gaertig said. Because few other proteins are modified in this way, Gaertig said he thinks that the tag may act like an interstate road sign, directing motor proteins to take their proper exits — to the cell’s nucleus or surface, for example.

The French team purified the new enzyme group from brains of mice, since it’s relatively abundant in that tissue. Nerve cells have a high level of polyglutamylation because of the intense traffic along microtubules that takes place as brain cells communicate. Still, the task took years because enzyme activity is high only in brains that are developing.

Gaertig’s group subsequently identified the active subunits of the enzyme complex and found the associated genes in many organisms, including humans. Gaertig and his UGA associates also showed that these enzymes modify just a portion of a microtubular highway, which supports the hypothesis that this process is a mechanism for directing cellular traffic.

The lab studied polyglutamylases from the single-celled pond organism Tetrahymena thermophila, which has abundant modified microtubules and manifests many of the same internal cell traffic patterns as do animal cells.

This work paves the way for more detailed studies of what polyglutamylate modification does and how it works, Gaertig said. In the long run, such research has implications for conditions such as polycystic kidney disease, male infertility, behavioral disorders and cancer, all of which involve defective microtubular highways.

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Research Communications, Office of the VP for Research, UGA
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